Harada Toshie, Kawaminami Hiromi, Miura Noriko N, Adachi Yoshiyuki, Nakajima Mitsuhiro, Yadomae Toshiro, Ohno Naohito
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy & Life Science, Japan.
Microbiol Immunol. 2006;50(9):687-700. doi: 10.1111/j.1348-0421.2006.tb03841.x.
SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. SCG shows antitumor activity and also enhances the hematopoietic response in cyclophosphamide (CY)-treated mice. In the present study, the molecular mechanism of the enhancement of the hematopoietic response was investigated. The levels of interferon-(IFN-)gamma, tumor necrosis factor-(TNF-)alpha, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-(IL-) 6 and IL-12p70 were significantly increased by SCG in CY-treated mice. GM-CSF production in the splenocytes from the CY-treated mice was higher than that in normal mice regardless of SCG stimulation. Neutralizing GM-CSF significantly inhibited the induction of IFN-gamma, TNF-alpha and IL-12p70 by SCG. The level of cytokine induction by SCG was regulated by the amount of endogenous GM-CSF produced in response to CY treatment in a dose-dependent manner. The expression of beta-glucan receptors, such as CR3 and dectin-1, was up-regulated by CY treatment. Blocking dectin-1 significantly inhibited the induction of TNF-alpha and IL-12p70 production by SCG. Taken together, these results suggest that the key factors in the cytokine induction in CY-treated mice were the enhanced levels of both endogenous GM-CSF production and dectin-1 expression.
SCG是皱盖乌芝中的一种主要的六分支1,3-β-D-葡聚糖。SCG具有抗肿瘤活性，还能增强环磷酰胺（CY）处理小鼠的造血反应。在本研究中，对造血反应增强的分子机制进行了研究。SCG可使CY处理小鼠体内的干扰素-（IFN-）γ、肿瘤坏死因子-（TNF-）α、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-（IL-）6和IL-12p70水平显著升高。无论有无SCG刺激，CY处理小鼠脾细胞中GM-CSF的产生均高于正常小鼠。中和GM-CSF可显著抑制SCG诱导的IFN-γ、TNF-α和IL-12p70。SCG诱导的细胞因子水平受CY处理后内源性GM-CSF产生量的剂量依赖性调节。CY处理可上调β-葡聚糖受体如CR3和dectin-1的表达。阻断dectin-1可显著抑制SCG诱导的TNF-α和IL-12p70产生。综上所述，这些结果表明，CY处理小鼠细胞因子诱导的关键因素是内源性GM-CSF产生水平和dectin-1表达的增强。
